Mobile phone interventions for tuberculosis should ensure access to mobile phones to enhance equity - a prospective, observational cohort study in Peruvian shantytowns.

OBJECTIVES: Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access among patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes. METHODS: In a prospective cohort study in Callao, Peru, we recruited and interviewed 2584 patients with tuberculosis between 2007 and 2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016 and 2017. Data were analysed using logistic regression and by calculating relative risks (RR). RESULTS: Between 2007 and 2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (P < 0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all P < 0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% vs. 13%, RR = 1.5; P = 0.001) or an adverse treatment outcome (29% vs. 23% RR = 1.3; P = 0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third. CONCLUSION: Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.

The seasonality of tuberculosis, sunlight, vitamin D, and household crowding.

BACKGROUND: Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years. METHODS: Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained. RESULTS: Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001). CONCLUSIONS: The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis.

Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru.

BACKGROUND: Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed "catastrophic" but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. METHODS AND FINDINGS: From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2-4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%-43%) in the least-poor houses versus 48% (95% CI = 36%-50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%-61%] versus 38% [95% CI = 34%-41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7-15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3-3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00-1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1-2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%-28%), similar to that of MDR TB (20% [95% CI = 14%-25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain "dis-saving" variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients. CONCLUSIONS: Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease. Please see later in the article for the Editors' Summary.

[River boats as a means of expansion of Aedes aegypti towards border zones of the peruvian amazon]. / Embarcaciones fluviales como medio de dispersión de Aedes aegypti hacia zonas fronterizas de la amazonia peruana.

OBJECTIVES.: To assess the entomological risk of Aedes aegypti in boats traversing border river routes in Loreto. MATERIALS AND METHODS.: The study population consisted of mosquitoes present in three boats covering border routes in Loreto. The entomological risk of Aedes was determined through ovitraps, the inspection of breeding sites, and the collection and taxonomic identification of adult mosquitoes. RESULTS.: The entomological risk varied according to the route and the season. A medium to very high entomological risk was identified in the high-water season and on the outward route to the border areas. The predominant vector population in the low-water season was Mansonia sp. (74.8%), Culex sp. (12.8%), and Aedes aegypti (0.4%); in the high-water season, Culex sp. (45.1%), Mansonia sp. (26.8%), and Aedes aegypti (19.7%). In no case did we find Aedes albopictus. CONCLUSIONS.: There is moderate to high entomological risk during the high-water season in riverboats traveling from Iquitos to the border areas of Loreto. Our results show that river boats are a means of expansion of Aedes aegypti.

OBJETIVOS.: Evaluar el riesgo entomológico de Aedes aegypti durante el recorrido fluvial en embarcaciones con rutas fronterizas de Loreto. MATERIALES Y MÉTODOS: . La población de estudio fueron los mosquitos presentes en tres embarcaciones con rutas fronterizas en Loreto. El riesgo entomológico de Aedes se determinó mediante ovitrampas, revisión de criaderos, colecta e identificación taxonómica de mosquitos adultos. RESULTADOS: . El riesgo entomológico varió según trayecto y época. Se identificó un riesgo entomológico medio a muy alto en época de creciente y en la ruta de ida hacia las zonas fronterizas. La población vectorial predominante en época de vaciante fue Mansonia sp. (74,8%), Culex sp. (12,8%) y Aedes aegypti (0,4%); en creciente predominó Culex sp. (45,1%), Mansonia sp. (26,8%) y Aedes aegypti (19,7%). En ningún caso se evidenció Aedes albopictus. CONCLUSIONES.: Existe riesgo entomológico de moderado a alto durante la etapa de creciente en las embarcaciones fluviales que viajan desde Iquitos hacia las zonas fronterizas de Loreto. Nuestros resultados evidencian que las embarcaciones fluviales son un medio de dispersión de Aedes aegypti.

Feasibility and Acceptability of a Text Message-Based Smoking Cessation Program for Young Adults in Lima, Peru: Pilot Study.

BACKGROUND: In Peru's urban communities, tobacco smoking generally starts during adolescence and smoking prevalence is highest among young adults. Each year, many attempt to quit, but access to smoking cessation programs is limited. Evidence-based text messaging smoking cessation programs are an alternative that has been successfully implemented in high-income countries, but not yet in middle- and low-income countries with limited tobacco control policies. OBJECTIVE: The objective was to assess the feasibility and acceptability of an short message service (SMS) text message-based cognitive behavioral smoking cessation program for young adults in Lima, Peru. METHODS: Recruitment included using flyers and social media ads to direct young adults interested in quitting smoking to a website where interested participants completed a Google Drive survey. Inclusion criteria were being between ages 18 and 25 years, smoking at least four cigarettes per day at least 6 days per week, willing to quit in the next 30 days, owning a mobile phone, using SMS text messaging at least once in past year, and residing in Lima. Participants joined one of three phases: (1) focus groups and in-depth interviews whose feedback was used to develop the SMS text messages, (2) validating the SMS text messages, and (3) a pilot of the SMS text message-based smoking cessation program to test its feasibility and acceptability among young adults in Lima. The outcome measures included adherence to the SMS text message-based program, acceptability of content, and smoking abstinence self-report on days 2, 7, and 30 after quitting. RESULTS: Of 639 participants who completed initial online surveys, 42 met the inclusion criteria and 35 agreed to participate (focus groups and interviews: n=12; validate SMS text messages: n=8; program pilot: n=15). Common quit practices and beliefs emerged from participants in the focus groups and interviews informed the content, tone, and delivery schedule of the messages used in the SMS text message smoking cessation program. A small randomized controlled pilot trial was performed to test the program's feasibility and acceptability; nine smokers were assigned to the SMS text message smoking cessation program and six to a SMS text message nutrition program. Participant retention was high: 93% (14/15) remained until day 30 after quit day. In all, 56% of participants (5/9) in the SMS text message smoking cessation program reported remaining smoke-free until day 30 after quit day and 17% of participants (1/6) in the SMS text message nutrition program reported remaining smoke-free during the entire program. The 14 participants who completed the pilot reported that they received valuable health information and approved the delivery schedule of the SMS text messages. CONCLUSIONS: This study provides initial evidence that a SMS text message smoking cessation program is feasible and acceptable for young adults residing in Lima.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.

BACKGROUND: Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS: In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS: In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION: Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

Rickettsial Disease in the Peruvian Amazon Basin.

Using a large, passive, clinic-based surveillance program in Iquitos, Peru, we characterized the prevalence of rickettsial infections among undifferentiated febrile cases and obtained evidence of pathogen transmission in potential domestic reservoir contacts and their ectoparasites. Blood specimens from humans and animals were assayed for spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) by ELISA and/or PCR; ectoparasites were screened by PCR. Logistic regression was used to determine associations between patient history, demographic characteristics of participants and symptoms, clinical findings and outcome of rickettsial infection. Of the 2,054 enrolled participants, almost 2% showed evidence of seroconversion or a 4-fold rise in antibody titers specific for rickettsiae between acute and convalescent blood samples. Of 190 fleas (Ctenocephalides felis) and 60 ticks (Rhipicephalus sanguineus) tested, 185 (97.4%) and 3 (5%), respectively, were positive for Rickettsia spp. Candidatus Rickettsia asemboensis was identified in 100% and 33% of the fleas and ticks tested, respectively. Collectively, our serologic data indicates that human pathogenic SFGR are present in the Peruvian Amazon and pose a significant risk of infection to individuals exposed to wild, domestic and peri-domestic animals and their ectoparasites.

Embarcaciones fluviales como medio de dispersión de Aedes aegypti hacia zonas fronterizas de la amazonia peruana / River boats as a means of expansion of Aedes aegypti towards border zones of the peruvian amazon

RESUMEN Objetivos. Evaluar el riesgo entomológico de Aedes aegypti durante el recorrido fluvial en embarcaciones con rutas fronterizas de Loreto. Materiales y métodos . La población de estudio fueron los mosquitos presentes en tres embarcaciones con rutas fronterizas en Loreto. El riesgo entomológico de Aedes se determinó mediante ovitrampas, revisión de criaderos, colecta e identificación taxonómica de mosquitos adultos. Resultados . El riesgo entomológico varió según trayecto y época. Se identificó un riesgo entomológico medio a muy alto en época de creciente y en la ruta de ida hacia las zonas fronterizas. La población vectorial predominante en época de vaciante fue Mansonia sp. (74,8%), Culex sp. (12,8%) y Aedes aegypti (0,4%); en creciente predominó Culex sp. (45,1%), Mansonia sp. (26,8%) y Aedes aegypti (19,7%). En ningún caso se evidenció Aedes albopictus. Conclusiones. Existe riesgo entomológico de moderado a alto durante la etapa de creciente en las embarcaciones fluviales que viajan desde Iquitos hacia las zonas fronterizas de Loreto. Nuestros resultados evidencian que las embarcaciones fluviales son un medio de dispersión de Aedes aegypti.

ABSTRACT Objectives. To assess the entomological risk of Aedes aegypti in boats traversing border river routes in Loreto. Materials and Methods. The study population consisted of mosquitoes present in three boats covering border routes in Loreto. The entomological risk of Aedes was determined through ovitraps, the inspection of breeding sites, and the collection and taxonomic identification of adult mosquitoes. Results. The entomological risk varied according to the route and the season. A medium to very high entomological risk was identified in the high-water season and on the outward route to the border areas. The predominant vector population in the low-water season was Mansonia sp. (74.8%), Culex sp. (12.8%), and Aedes aegypti (0.4%); in the high-water season, Culex sp. (45.1%), Mansonia sp. (26.8%), and Aedes aegypti (19.7%). In no case did we find Aedes albopictus. Conclusions. There is moderate to high entomological risk during the high-water season in riverboats traveling from Iquitos to the border areas of Loreto. Our results show that river boats are a means of expansion of Aedes aegypti.

Tuberculin skin-test reactions are unaffected by the severity of hyperendemic intestinal helminth infections and co-infections.

The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (> or = 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species.